Stefan Grossauer

Medical University of Vienna | MedUni Vienna · Department of Neurosurgery

BACKGROUND Despite the availability of targeted therapies, gliomas carrying the BRAFV600E mutation remain challenging to treat. Combined pharmacologic BRAFV600E and MEK inhibition is clinically used in patients with BRAFV600E mutant gliomas, but primary and acquired resistance is reported in ~70% of high-grade glioma patients. OBJECTIVES To gain m...

BRAF V600E-mutated glioma patients are in urgent need of new treatments, since standard chemoradiotherapy and surgery achieves tumor control in less than 30% of patients. BRAF and MEK inhibitor combinations have shown promising results against several types of BRAF V600E mutated cancers. Patients with high-grade BRAF V600E mutated gliomas frequentl...

BACKGROUND Despite successes, clinical MAPK pathway inhibitors show limited anti-tumor activity in the majority of patients with BRAF-mutant high-grade glioma. Because of the presence of higher fraction of CD8+ tumor-infiltrating T cells in MAPK pathway-altered glioma, we explored the possibility that combined BRAF and MEK inhibition with immune ch...

p>Pediatric low-grade gliomas (pLGG) are the most common central nervous system (CNS) tumor in children. Although the majority of pLGG has unregulated MAPK pathway activity, and clinical MAPK pathway inhibitors are available, pLGG treatment remains challenging. Tumor progression, rebound, and therapy resistance limit the success of MAPK pathway inh...

Background BRAF alterations frequently occur in pediatric low-grade gliomas. Previously, we showed that dabrafenib and trametinib (D+T) that target MAPK pathway can mediate the antitumor effect in a preclinical model of BRAF-mutant glioma (PMC5342782). Here, we further investigate the effect of MAPK pathway inhibitors on cancer cells and tumor-infi...

Pediatric low-grade glioma (pLGG), the most common brain cancer in children, is difficult to treat especially at recurrence. The BRAF V600E mutation is the second most common mutation in pLGG, and in a high-risk group for progression is associated with deletion of the tumor suppressor CDKN2A. A better understanding of the factors contributing to pr...

Pediatric patients with gliomas expressing the constitutively active BRAFV600E-mutant kinase are candidates for clinical trials for small molecule inhibitors specific for BRAFV600E (BRAFi) and MEK (MEKi) (Grossauer et al; Oncotarget 2016, 15:75839). Clinical results from combined BRAF and MEK inhibition (BRAFi+ MEKi) showed promising results with o...

Decompressive craniectomy (DC) is an accepted surgical technique for reducing life-threatening levels of intracranial pressure. Remodelling the cranial vault following DC can constitute a reconstructive challenge and is known to carry significant morbidity. The aim of our study was to evaluate acrylic versus autologous cranioplasty with regard to s...

BRAFV600E mutations are frequent in pediatric gliomas. We previously showed antitumor activity when using BRAF and/or MEK inhibitors against BRAFV600E glioma syngeneic grafts (Grossauer et al., Oncotarget 2016;7:775839). While early clinical trial reports suggest an encouraging response rate to BRAFV600E inhibitors alone (Burger et al., Oncol Rep 2...

Even in the MRI era lumbar nerve root anomalies in patients with lumbar radiculopathies are still frequently un- or misdiagnosed and usually discovered during spine surgery only. The existing literature suggests that patients with lumbar nerve root anomalies are especially prone to develop radiculopathies and suffering operative complications. Ther...

BRAFV600E mutations are frequent in pediatric gliomas. We previously showed anti-tumor activity when using BRAF and/or MEK inhibitors against BRAFV600E glioma xenografts. While early clinical trial reports suggest an encouraging response rate, a significant fraction of tumors shows no therapy reponse. Using expression arrays on 30 pediatric gliomas...

Inhibitors of BRAFV600E kinase are currently under investigations in preclinical and clinical studies involving BRAFV600E glioma. Studies demonstrated clinical response to such individualized therapy in the majority of patients whereas in some patients tumors continue to grow despite treatment. To study resistance mechanisms, which include feedback...

Background Early detection of vasospasm (VS) following aneurysmal subarachnoid hemorrhage (aSAH) is vital to trigger therapy and to prevent infarction and subsequent permanent neurological deficit. Although motor evoked potentials (MEPs) are a well-established method for intraoperative detection of cerebral VS and cerebral ischemia during aneurysm...

Glioma stem cells (GSC) are postulated to provide a reservoir of cells with self-renewal capabilities, sustain tumor growth by generating differentiated non-stem tumor cells and may be responsible for recurrences after chemo-, radio- and surgical therapy. Elimination of the GSC population is regarded as a key to successful treatment of glioma, but...

The treatment of glioblastoma (GBM) remains challenging in part due to the presence of stem-like tumor-propagating cells that are resistant to standard therapies consisting of radiation and temozolomide. Among the novel and targeted agents under evaluation for the treatment of GBM are BRAF/MAPK inhibitors, but their effects on tumor-propagating cel...

BACKGROUND: Early detection of vasospasm (VS) following aneurysmal subarachnoid hemorrhage (aSAH) is vital to trigger therapy and to prevent infarction and subsequent permanent neurological deficit. Although motor evoked potentials (MEPs) are a well-established method for intraoperative detection of cerebral VS and cerebral ischemia during aneurysm...

In the last decade evidence has accumulated that suggests that the cerebellum is involved not only in motor but also in behavioral and cognitive functions. A myriad of anatomical, clinical and imaging studies support that assumption. The lengthened survival of patients with cerebellar tumors has also brought an increased awareness of neurocognitive...

The most appropriate surgical technique for posterior fossa decompression in Chiari malformation (CM) remains a matter of debate. Intraoperative electrophysiological studies during posterior fossa decompression of Type I CM (CM-I) aim to shed light on the entity's pathomechanism as well as on the ideal extent of decompression. The existing reports...

Cells in the central nervous system rely almost exclusively on aerobic metabolism. Oxygen deprivation, such as injury-associated ischemia, results in detrimental apoptotic and necrotic cell loss. There is evidence that repetitive hyperbaric oxygen therapy (HBOT) improves outcomes in traumatic brain-injured patients. However, there are no experiment...

Intrathecal drug delivery systems are an option for selected patients with chronic pain. Complications such as intrathecal catheter-tip inflammatory masses are already reported in literature. In the present case report we describe a patient suffering from neuropathic pain located on the anterior aspects of both thighs following failed back surgery....

Introduction: Intraoperative neurophysiology has moved giant steps forward over the past 15 years thanks to the advent of techniques aimed to reliably assess the functional integrity of motor areas and pathways. Intraoperative neurophysiological techniques: Motor evoked potentials recorded from the muscles and/or the spinal cord (D-wave) after t...

Purpose: For patients with large vestibular schwannomas (VS) three major treatment options are available: microsurgery, stereotactic radiation, and combined treatment. For the present, microsurgery represents the standard treatment method for large VS, but high-risk patients facing additional cardiopulmonary problems are alternatively offered stere...